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Identification and characterization of CMP-NeuAc:GalNAc-IgA1 alpha2,6-sialyltransferase in IgA1-producing cells

Raska, Milan; Moldoveanu, Zina; Suzuki, Hitoshi; Brown, Rhubell; Kulhavy, Rose; Andrasi, Judit; Hall, Stacy; Vu, Huong L; Carlsson, Fredric LU and Lindahl, Gunnar LU , et al. (2007) In Journal of Molecular Biology 369(1). p.69-78
Abstract
Glycosylation defects occur in several human diseases. In IgA nephropathy, IgA1 contains O-glycans that are galactose-deficient and consist mostly of core 1 alpha2,6 sialylated N-acetylgalactosamine, a configuration suspected to prevent beta1,3 galactosylation. We confirmed the same aberrancy in IgA1 secreted by the human DAKIKI B cell line. Biochemical assays indicated CMP-NeuAc:GalNAc-IgA1 alpha2,6-sialyltransferase activity in this cell line. However, a candidate enzyme, ST6-GalNAcI, was not transcribed in DAKIKI cells, B cells isolated from blood, or Epstein-Barr virus (EBV)-immortalized IgA1-producing cells from the blood of IgAN patients and healthy controls. Instead, ST6-GalNAcII transcription was detected at a high level.... (More)
Glycosylation defects occur in several human diseases. In IgA nephropathy, IgA1 contains O-glycans that are galactose-deficient and consist mostly of core 1 alpha2,6 sialylated N-acetylgalactosamine, a configuration suspected to prevent beta1,3 galactosylation. We confirmed the same aberrancy in IgA1 secreted by the human DAKIKI B cell line. Biochemical assays indicated CMP-NeuAc:GalNAc-IgA1 alpha2,6-sialyltransferase activity in this cell line. However, a candidate enzyme, ST6-GalNAcI, was not transcribed in DAKIKI cells, B cells isolated from blood, or Epstein-Barr virus (EBV)-immortalized IgA1-producing cells from the blood of IgAN patients and healthy controls. Instead, ST6-GalNAcII transcription was detected at a high level. Expression of the ST6-GalNAcII gene and activity of the CMP-NeuAc:GalNAc-IgA1 alpha2,6-sialyltransferase were higher in IgA1-producing cell lines from IgAN patients than in such cells from healthy controls. These data are the first evidence that human cells that lack ST6-GalNAcI can sialylate core 1 GalNAc-Ser/Thr. (Less)
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type
Contribution to journal
publication status
published
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in
Journal of Molecular Biology
volume
369
issue
1
pages
69 - 78
publisher
Elsevier
external identifiers
  • pmid:17418236
  • wos:000246661100006
  • scopus:34247394150
ISSN
1089-8638
DOI
10.1016/j.jmb.2007.03.002
language
English
LU publication?
yes
id
1f0a1477-7b6c-49e4-be0d-787c2735d5f6 (old id 1137733)
date added to LUP
2008-08-15 14:22:36
date last changed
2017-09-17 07:43:18
@article{1f0a1477-7b6c-49e4-be0d-787c2735d5f6,
  abstract     = {Glycosylation defects occur in several human diseases. In IgA nephropathy, IgA1 contains O-glycans that are galactose-deficient and consist mostly of core 1 alpha2,6 sialylated N-acetylgalactosamine, a configuration suspected to prevent beta1,3 galactosylation. We confirmed the same aberrancy in IgA1 secreted by the human DAKIKI B cell line. Biochemical assays indicated CMP-NeuAc:GalNAc-IgA1 alpha2,6-sialyltransferase activity in this cell line. However, a candidate enzyme, ST6-GalNAcI, was not transcribed in DAKIKI cells, B cells isolated from blood, or Epstein-Barr virus (EBV)-immortalized IgA1-producing cells from the blood of IgAN patients and healthy controls. Instead, ST6-GalNAcII transcription was detected at a high level. Expression of the ST6-GalNAcII gene and activity of the CMP-NeuAc:GalNAc-IgA1 alpha2,6-sialyltransferase were higher in IgA1-producing cell lines from IgAN patients than in such cells from healthy controls. These data are the first evidence that human cells that lack ST6-GalNAcI can sialylate core 1 GalNAc-Ser/Thr.},
  author       = {Raska, Milan and Moldoveanu, Zina and Suzuki, Hitoshi and Brown, Rhubell and Kulhavy, Rose and Andrasi, Judit and Hall, Stacy and Vu, Huong L and Carlsson, Fredric and Lindahl, Gunnar and Tomana, Milan and Julian, Bruce A and Wyatt, Robert J and Mestecky, Jiri and Novak, Jan},
  issn         = {1089-8638},
  language     = {eng},
  number       = {1},
  pages        = {69--78},
  publisher    = {Elsevier},
  series       = {Journal of Molecular Biology},
  title        = {Identification and characterization of CMP-NeuAc:GalNAc-IgA1 alpha2,6-sialyltransferase in IgA1-producing cells},
  url          = {http://dx.doi.org/10.1016/j.jmb.2007.03.002},
  volume       = {369},
  year         = {2007},
}